BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE194004 | GEO | 2022/05/02
REPOSITORIES: GEO
Similar Datasets
Project description:BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states
| PRJNA798725 | ENA
Project description:Enteroendocrine cells (EECs) control a wide range of physiological processes linked to metabolism1. We show that EEC hormones are differentially expressed between crypts (for example, Glp1) and villi (for example, secretin). As demonstrated by single-cell mRNA sequencing using murine Lgr5+ cell-derived organoids, BMP4 signals alter the hormone expression profiles of individual EECs to resemble those found in the villus. Accordingly, BMP4 induces hormone switching of EECs migrating up the crypt-villus axis in vivo. Our findings imply that EEC lineages in the small intestine exhibit a more flexible hormone repertoire than previously proposed. We also describe a protocol to generate human EECs in organoids and demonstrate a similar regulation of hormone expression by BMP signalling. These findings establish alternative strategies to target EECs with therapeutically relevant hormone production through BMP modulation.
| S-EPMC6276989 | biostudies-literature
Project description:By chemical modulation of the PKA/CREB and BMP pathways in isolated AGM VE-cadherin+ cells from mid-gestation embryos, we demonstrate that PKA/CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors and is dependent on secreted BMP ligands through the type I BMP receptor. We used microarray to document upregulation of PKA/CREB-BMP pathway as well as global BMP target upregulation upon PKA/CREB activation. Isolated VE+ cells from E11.5 AGM were treated with BMP4 (4ng/ml), forskolin (25uM) or both for 8 hours before RNA isolation.
2015-03-30 | E-GEOD-62517 | biostudies-arrayexpress
Project description:By chemical modulation of the PKA/CREB and BMP pathways in isolated AGM VE-cadherin+ cells from mid-gestation embryos, we demonstrate that PKA/CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors and is dependent on secreted BMP ligands through the type I BMP receptor. We used microarray to document upregulation of PKA/CREB-BMP pathway as well as global BMP target upregulation upon PKA/CREB activation.
2015-03-30 | GSE62517 | GEO
Project description:The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgf. Here we show that individual Bmp ligands and Tgf drive distinct enterocytic programs specific to villus zonation. Bmp4 is expressed mainly from the centre to the upper part of the villus, and it activates preferentially genes connected to lipid uptake and metabolism. In contrast, Bmp2 is produced by villus-tip mesenchymal cells, and it influences the adhesive properties of villus-tip epithelial cells and the expression of antimicrobial peptides. Hence, Bmp2 promotes the terminal enterocytic differentiation at the villus-tip. Additionally, Tgf induces an epithelial gene expression programs similar to that triggered by Bmp2. The inhibition of Bmp receptor type I in vivo and using intestinal organoids lacking Smad4 revealed that Bmp2-driven villus-tip program is activated by a canonical Smad-dependent mechanism. Finally, we established an organoid cultivation system that enriches for villus-tip enterocytes and thereby better mimics the cellular composition of the intestinal epithelium. Altogether our data suggest that not only Bmp gradient, but also the activity of individual Bmp drives specific enterocytic programs.
2023-07-01 | GSE216699 | GEO
Project description:Mindbomb1 is a Novel Negative Regulator of BMP Signaling.
2024-07-02 | MSV000095215 | MassIVE
Project description:BMP (bone morphogenetic protein) signaling plays essential roles in the regulation of early tooth development. It is well acknowledged that with binding of extracellular BMP ligands to the type I and type II transmembrane serine/threonine kinase receptor complexes when triggering of the BMP canonical signaling pathway, receptor activated Smad1/5/8 in cytoplasm bind to Smad4, the central mediator of the canonical BMP signaling pathway, to form transfer complexes for entering the nucleus and regulating target gene expression. However, our recent studies reveal the functional operation of a novel BMP mediated signaling pathway named as the atypical BMP canonical signaling pathway in mouse developing tooth, which is Smad1/5/8 dependent but Smad4 independent. In the current study, we investigated whether this atypical BMP canonical signaling is conserved in human odontogenesis. We showed that pSmad1/5/8 is required for expression of MSX1, a well-defined BMP signaling target gene, in human dental mesenchyme, but the typical BMP canonical signaling is indeed not operating in the early human developing tooth, as assessed by the absence of pSMAD1/5/8-SMAD4 complexes in the dental mesenchyme and expression of MSX1 and translocation of pSMAD1/5/8 induced by BMP4 protein is SMAD4-independent in dental mesenchymal cells. Moreover, RNA-Seq data sets comparing the transcriptome profiles of human dental mesenchymal cells with and without SMAD4 knockdown by siRNA displays unchanged expression profiles of pSMAD1/5/8 downstream target genes, further affirming the functional operation of the atypical canonical BMP signaling pathway in a manner of SMAD1/5/8-dependent but SMAD4-independent in the dental mesenchyme during early odontogenesis.
2021-09-30 | GSE179474 | GEO
Project description:Patterning of the vertebrate anteroposterior (AP) axis proceeds temporally from anterior to posterior. How dorsoventral (DV) axial patterning relates to AP temporal patterning is unknown. We examined the temporal activity of BMP signaling in patterning ventrolateral cell fates along the AP axis, using transgenes that rapidly turn "off" or "on" BMP signaling. We show that BMP signaling patterns rostral DV cell fates at the onset of gastrulation, whereas progressively more caudal DV cell fates are patterned at progressively later intervals during gastrulation. Increased BMP signal duration is not required to pattern more caudal DV cell fates; rather, distinct temporal intervals of signaling are required. This progressive action is regulated downstream of, or in parallel to, BMP signal transduction at the level of Smad1/5 phosphorylation. We propose that a temporal cue regulates a cell's competence to respond to BMP signaling, allowing the acquisition of a cell's DV and AP identity simultaneously.
| S-EPMC2266782 | biostudies-literature
Project description:The mesodermal precursor populations for different internal organ systems are specified during gastrulation by the combined activity of extracellular signaling systems such as BMP, Wnt, Nodal, and FGF. The BMP, Wnt and Nodal signaling requirements for the differentiation of specific mesoderm subtypes in mammals have been mapped in detail, but which mesodermal cell types depend on FGF signaling is not precisely known. It is also not clear how FGF signaling modulates the activity of orthogonal signaling systems involved in mesoderm differentiation. Here, we address these questions by analyzing the effects of targeted signaling manipulations in differentiating stem cell populations with single cell resolution. We identify opposing functions of BMP and FGF, and map the boundary between FGF-dependent and -independent mesodermal lineages. Stimulation with exogenous FGF boosts the expression of endogenous Fgfs while repressing Bmp ligands. This intercellular positive autoregulation of FGF signaling coupled to the repression of BMP signaling may contribute to the specification of reproducible and coherent cohorts of cells with the same identity via a community effect, both in the embryo and in synthetic embryo-like systems.
2023-03-24 | GSE228061 | GEO
Project description:This model couples BMP morphogen gradient formation with Smad signaling in zebrafish and reproduces Fig.3B of the referenced paper. mBMP4 diffuses and forms a morphogen gradient in the host tissue where differential signal transduction kinetics for pSmad2 versus pSmad5 lead to narrow (pSmad2) versus wide (pSmad5) signal activity ranges in response to the same morphogen gradient (mBMP4) as input. The model file is in MorpheusML format and can be opened in the free, open-source multicellular modeling software Morpheus (https://morpheus.gitlab.io) to simulate the time course (movie) of the spatio-temporal dynamics. Further optional plots of the radial solution profile and the time courses of mean concentrations over the domain are included and temporarily inactivated in the model file, in section Analysis.
2021-10-06 | MODEL2012070002 | BioModels